multiple ways and expanded before reinfusion. Clinically, this approach has shown high efficacy, however, unlike standard PCVs, pulsed APCs are extremely costly and labour-intensive and require expert-level technicians in order to generate the raw materials for the vaccine, making large scale treat- ment very difficult to achieve. One of the main issues with using nucleotide or SLP-based PCVs are the delivery of neoantigens to APCs within patients’ lymphatic tissue in order for neoeptiopes to be presented on MHC to bind to TCRs and initiate an immune cascade. In order to direct neoantigen DNA, mRNA, or SLPs to APCs and/or lymphatic tissue, researchers have been util- ising biomaterial-assisted PCVs. These vehicles eliminate many of the cons of nucleotide or peptide based PCVs by using a novel biomaterial to deliver the neoantigen in tandem with adjuvants and direct targeting for enhanced cancer vaccines. There are many different kinds of biomaterial- assisted neoantigen vaccines, but they usually con- tain an encapsulating agent to encompass the neoantigens themselves (nucleotide or SLP), an adjuvant or a bacterial/viral particle in order to boost the immune response, and a targeting agent, such as an APC ligand or an antibody to make sure that the PCV is delivered to APCs and the lymphat- ic system. A main benefit of using these delivery vehicles is that once the mechanics of the delivery format are figured out, a clinician can interchange neoantigens based on the genetic make-up of indi- vidual patient’s tumours, making PCV delivery much easier. However, it takes a lot of time and research in order to generate a novel PCV modali- ty, as there are unlimited options within a design to choose from. Conclusion Personalised cancer vaccines are able to evade can- cer’s natural immune defences to trick patients’ immune systems to target and kill tumours based on a subset of rare, cancer-specific, somatic muta- tions. In combination with other immunotherapies such as checkpoint inhibitors and standard meth- ods of care such as chemotherapy and radiation, despite being young in the clinic, PCVs have shown great efficacy in a very short period of time. Given the large range of delivery modalities for PCVs, and the individuality of personalised immunotherapies, the combinations of treatments seem endless. However, with the direction PCV research is going today, it is only a matter of time The pros and cons of biomaterial-assisted PCVs
before personalised medicine is placed at the fore- front of cancer treatment, as a possible cure for the incurable. DDW
Dr Samantha Zaroff received her PhD in 2017 from Rowan University focusing on the molecular mechanisms of neurodegenerative disease. Dr Zaroff then became the marketing specialist for GenScript’s custom antibody and antibody drug services lines. Dr Zaroff currently works as the product manager of neoantigen peptide synthesis services at GenScript.
Drug DiscoveryWorld Summer 2020
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